Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
during maturation into mature RBCs in most dogs ( Maede
and Inaba, 1985 ). Consequently, RBCs from most dogs
have low potassium concentrations owing to the absence
of Na ,K -pump activity ( Parker, 1977 ). However, some
Japanese mongrel dogs, some Japanese Akita dogs, some
Japanese Shiba dogs, and some Korean dogs (especially
Jindo dogs) have HK RBCs, because the Na ,K -pump is
retained in mature RBCs ( Degen, 1987 ; Fujise et al. , 1997a ;
Maede et al. , 1983, 1991 ; Yamato et al. , 1999 ). Clinically,
these dogs appear normal. This trait is inherited in an autosomal
recessive manner. HK dog RBCs have higher MCV,
lower MCHC, and similar MCH values compared to LK
dogs of the same breed, suggesting an increase in cell water
(Maede et al. , 1983 ). Although dogs with HK RBCs are
not anemic, their RBCs have shortened life spans ( Maede
and Inaba, 1987 ), and some dogs have slightly increased
reticulocyte counts ( Maede et al. , 1983 ). The osmotic fragility
was increased in mongrel dogs ( Maede et al. , 1983 ),
but not in Jindo dogs ( Yamato et al. , 1999 ).
RBCs from most of these dogs also have high GSH,
glutamate, glutamine, and aspartate concentrations secondary
to increased glutamate and aspartate uptake. GSH concentration
is increased five to seven times normal because
the feedback inhibition of GCS by GSH is released by the
markedly increased glutamate concentration ( Maede et al. ,
1982 ). These HK , high GSH RBCs promote Babesia
gibsoni replication compared to LK , normal GSH RBCs
(Yamasaki et al. , 2005 ).
Dog RBCs have a high affinity Na -dependent transport
system for glutamate and aspartate ( Young, 1983 ).
The increased transport of these amino acids into RBCs
of affected dogs apparently occurs as a consequence of the
Na and K concentration gradients produced by the presence
of a Na ,K -ATPase activity three times higher than
that of human RBCs ( Inaba and Maede, 1984 ). The glycolytic
rate of HK dog RBCs is about twice that of LK
cells, because greater ATP production is required to provide
energy for active cation transport by the Na ,K -pump and
for increased GSH synthesis ( Maede and Inaba, 1987 ).
The high GSH concentration in the HK dog RBCs
provides increased protection against oxidative damage
induced by acetylphenylhydrazine ( Ogawa et al. , 1992 )
but increased susceptibility to oxidative damage induced
by 4-aminophenyl disulfide ( Maede et al. , 1989 ), n-propylthiosulfate
( Inaba, 2000 ), and onions ( Yamoto and Maede,
1992 ). Evidence suggests that the increased GSH concentration
potentiates the generation of superoxide through
its redox reaction with organosulfur compounds present in
onions ( Munday et al. , 2003 ).
A variant of this HK RBC disorder has been reported in
dogs that lack GSH accumulation ( Fujise et al. , 1993, 1997b ).
It was suggested that these dogs had a defect in amino acid
metabolism in addition to the persistence of the Na ,K -
pump. Potassium concentration was estimated to be increased
in RBCs from a Chinese shar-pei dog that was evaluated
to determine the cause of pseudohyperkalemia ( Battison,
2007 ). Increased osmotic fragility was present along with
some macrocytic hypochromic RBCs. RBC Na ,K -ATPase
activity and GSH concentration were not assayed.
C . Miscellaneous Abnormalities
1 . Familial Nonspherocytic Hemolytic Anemia in
Poodles
A nonspherocytic hemolytic anemia occurs in poodles
(Randolph et al. , 1986 ). An autosomal dominant trait with
incomplete penetrance mode of transmission was suggested.
Affected animals had severe persistent macrocytic hypochromic
anemia (hematocrits 13% to 31%) with marked
reticulocytosis. As in dogs with PK deficiency, myelofibrosis,
osteosclerosis, and excess iron deposition in hepatocytes
and mononuclear phagocytes were observed at necropsy.
One dog died when 2.5 years old with liver failure. Despite
extensive studies, the defect in this disorder could not be
determined, but PK deficiency cannot be ruled out.
2 . Hereditary Nonspherocytic Hemolytic Anemia in
Beagles
A mild hemolytic anemia with reticulocytosis, slightly
increased RBC osmotic fragility, shortened RBC life span,
and normal RBC morphology have been reported in beagle
dogs ( Maggio-Price et al. , 1988 ). Studies of RBC enzymes,
membrane protein electrophoresis, and Hb failed to identify
a defect. Decreased calcium pump ATPase activity
( Hinds et al. , 1989 ) and accelerated RBC swelling under
osmotic stress ( Pekow et al. , 1992 ) have been reported in
RBCs from anemic dogs, but these abnormalities may be
the consequence of an unknown membrane defect rather
than representing primary abnormalities. Although the
etiology remains elusive, this abnormality appears to be
transmitted as an autosomal recessive trait.
3 . Familial Erythrocytosis in Cattle
Marked erythrocytosis (hematocrits 60% to 80%) has
been described in calves from a highly inbred Jersey herd
(Tennant et al. , 1967, 1969 ). Affected calves had normal Hb
types and arterial blood gas values. As with normal calves,
hematocrits were within the adult range at birth, fell during
the first month of life, and then increased during the next
2 months. In contrast to normal calves, however, the
hematocrit continued to increase in affected calves until 6 to
7 months of age. The majority of affected calves died during
this time. Hematocrits of surviving animals returned slowly
to normal by maturity. Serum of affected calves lacked measurable
Epo but contained a growth factor that appeared to
enhance Epo activity in vitro ( Van Dyke et al. , 1968 ). The
pathogenesis of this disorder may involve an abnormally
controlled increased RBC production in response to the
anemia of the neonate ( Tennant et al. , 1969 ). A variety of
familial and congenital erythrocytosis syndromes have been